Abstract 18484: Cardiovascular Progenitors Derived from Induced Pluripotent Stem Cells (iPS) — A Promising Cell Source for Myocardial Restoration
Background/Aim: Induced pluripotent stem (iPS) cells are obtained from somatic cells by reprogramming the genome to a pluripotent state. Cardiovascular progenitor cells derived from iPS cells might be useful for autologous cellular cardiomyoplasty. Flk1 has been described as an early mesodermal and precardiac cell surface marker. The aim of the present study was to evaluate the potential of murine iPS cell derived Flk1+ progenitor cells to give rise to cardiovascular cell types in vitro and in vivo and to improve cardiac function following myocardial infarction in mice.
Material and Methods: Flk1+ progenitor cells were FACS-sorted from differentiating murine iPS cells. They were further cultivated for in vitro characterization or injected into the ischemic myocardium of LAD-ligated mice. Infarcted animals were treated with placebo (PBS, Group A, n=10) or Flk1+ progenitor cells (Group B, N=11, 5x10^5 cells). They underwent conductance catheter (CC) and MRI evaluation two weeks postoperatively to determine functional cardiac outcome. In vivo differentiation was evaluated by immunhistochemistry.
Results: Murine iPS cell derived Flk1+ progenitor cells gave rise to cardiac troponin T expressing cardiomyocytes, alpha-smooth muscle actin positive cells and CD31 expressing endothelial cells in vitro and in vivo. Treatment with Flk1+ iPS progenitor cells resulted in a favorable myocardial remodeling as evaluated by CC analysis and MRI: Compared to controls cell treated animals showed a significantly decreased cardiac volume load (enddiastolic volume [EDV]: 27±3μl vs. 19±2μl, p<0.05) and an improved left ventricular function (left ventricular ejection fraction [LV-EF]: 16±1% vs. 31±3%, p<0.01).
Conclusion: iPS cell derived Flk1+ progenitor cells differentiate into cells of cardiovascular lineages in vitro and in vivo and improve cardiac function after acute myocardial infarction. They are a promising autologous cell source for myocardial restoration in ischemic heart failure.
- © 2010 by American Heart Association, Inc.